Human herpesvirus 6 (HHV-6), discovered 4 years ago, is most closely related to CMV. Serologic studies indicate that nearly everyone becomes infected early in childhood, probably resulting in lifelong latency. HHV-6 is readily detected in peripheral blood mononuclear cells (PBMC) from children with roseola and in a subset of immunocompromised individuals. This proposal describes studies that will examine the time course and anatomic sites of HHV-6 infection, reactivation and latency in 3 immunosuppressed groups: the largest group will be bone marrow transplant (BMT) patients, and 2 smaller groups are comprised of liver transplant and heart transplant patients (Specific Aim 1). Preliminary data suggests that BMT patients with lung disease have HHV-6 in lung tissue. This finding will be expanded to investigate the etiologic role of HHV-6 in BMT patients with lung disease (Specific Aim 2). The subjects will have normal age and sex matched controls, who will also serve to better define the natural history of HHV-6 infection in immunocompetent people (Specific Aim 3). The prevalence of reinfection versus reactivation in BMT patients will be studied after developing a polymerase chain reaction (PCR) method for strain specific identification of HHV-6 in clinical samples (Specific Aim 4). Saliva, PBMC, urine, and biopsy tissue will be collected on a regular basis over 6 months and screened using semi-quantitative HHV-6 specific PCR. Positive samples will be further examined using HHV-6 RNA directed PCR, in situ hybridization and immunocytochemistry. HHV-6 culture will be performed in selected cases. An HHV-6 EIA serology will be used to document the serologic status at each time point when other samples are taken. The proposed studies will better define the natural history of HHV- 6 infections in immunocompromised and normal individuals. Specific etiologic relationships between HHV-6 infection and clinical disease will be sought in the immunocompromised subjects, who have demonstrated a propensity for exhibiting symptoms from other herpesvirus infections.